The intracellular parasite Toxoplasma gondii is a category B priority pathogen that is a major food borne pathogen of humans and livestock, but very little is known about how the parasite is recognized and controlled by the immune system. In Aim 1 we will examine the impact of innate immune signaling pathways on T. gondii infection using fibroblasts, dendritic cells, macrophage and mice containing defined genetic lesions. Particular emphasis will be placed on TRAIL-R and FADD (in collaboration with Project 2) and NK cells and the NK ligand NKG2D (in collaboration with Project 3). In Aim 2 we will identify the major natural antigens recognized by CDS T cells during Toxoplasma infection. We hypothesize that the parasite antigens recognized by CDS T cells will vary depending on the stage of infection and the type of antigen presenting cells involved. In Aim 3, we will examine the impact of innate immune responses and CD4 T cells on the response of CDS T cells. We will quantitate CDS T cell responses to particular antigens in mice lacking CD4 T cells or the innate immune pathways identified in Aim 1. We will also use 2-photon imaging to examine the dynamic aspects of immune responses in Aims 1 and 3.